RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy.
Cytokine-Induced Memory-Like NK Cells: Emerging strategy for AML immunotherapy.
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急性髓系白血病(AML)是由骨髓和外周血髓系前体细胞恶性扩增导致的异质性疾病。强化化疗和造血干细胞移植(HSCT)改善了AML患者结局,但复发和疗效不佳仍很常见。近年来,研究人员迅速探索新的治疗策略以优化结局。其中,自然杀伤(NK)细胞免疫疗法因其免疫监视作用及靶向AML原始细胞的能力而受到临床关注。NK细胞是细胞毒性先天淋巴细胞,可通过产生促炎细胞因子和直接诱导细胞毒作用,介导抗病毒及抗肿瘤应答。NK细胞通常被认为寿命较短、应答非特异性,这限制了其临床应用;细胞因子诱导的记忆样(CIML)NK细胞的发现则有望克服这些挑战。经IL-12/15/18细胞因子组合预活化的NK细胞可具有长期存活能力和适应性免疫特征,称为CIML-NK细胞。既往研究证实,CIML-NK用于癌症治疗安全且结局良好。本文综述CIML-NK细胞治疗AML的当前应用、挑战和机遇。
Acute myeloid leukemia (AML) is a heterogeneous disease developed from the malignant expansion of myeloid precursor cells in the bone marrow and peripheral blood. The implementation of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) has improved outcomes associated with AML, but relapse, along with suboptimal outcomes, is still a common scenario. In the past few years, exploring new therapeutic strategies to optimize treatment outcomes has occurred rapidly. In this regard, natural killer (NK) cell-based immunotherapy has attracted clinical interest due to its critical role in immunosurveillance and their capabilities to target AML blasts.
NK cells are cytotoxic innate lymphoid cells that mediate anti-viral and anti-tumor responses by producing pro-inflammatory cytokines and directly inducing cytotoxicity. Although NK cells are well known as short-lived innate immune cells with non-specific responses that have limited their clinical applications, the discovery of cytokine-induced memory-like (CIML) NK cells could overcome these challenges.
NK cells pre-activated with the cytokine combination IL-12/15/18 achieved a long-term life span with adaptive immunity characteristics, termed CIML-NK cells. Previous studies documented that using CIML-NK cells in cancer treatment is safe and results in promising outcomes. This review highlights the current application, challenges, and opportunities of CIML-NK cell-based therapy in AML.
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